Stimuli-responsive, or “smart materials,” have found wide acceptance across a variety of fields due to their ability to exhibit a significant change in physical properties as a result of a minor change in external stimuli such as light, electric potential, pH, redox, magnetic field, pressure, or temperature. Temperature sensitive polymers, mainly represented by poly(N-isopropylacrylamide) (PNIPAM)3-4 and polyoxazolines (POx)5-6, undergo a thermally induced reversible hydrophobicity change at a lower critical solution temperature (LCST). Above the LCST, certain thermoresponsive polymers such as PNIPAM undergo a coil-globule transition that results in significant dehydration of the polymer. The dehydrated polymers then aggregate due to hydrophobic interactions and the solution optically changes from clear to opaque. The temperature at which this observable macroscopic transformation occurs is defined as the cloud point temperature (Tcp) and is often used as a qualitative measure of the LCST. Not all temperature responsive polymers undergo the coil-globule transition exhibited by PNIPAM. Instead, some polymers display an incomplete dehydration when brought above the LCST. The partially dehydrated polymers then separate into polymer-rich coacervate droplets within a polymer-deficient liquid phase. Similar to coil-globule transition-type polymers, coacervate-type polymers exhibit a thermally reversible cloud point in solution. Coacervate-type polymers are particularly attractive from a biomaterials standpoint since their incomplete dehydration leads to minimal conformational change as compared to coil-globule polymers. This prevents coacervate-type polymers from damaging sensitive biomolecules and thus allows them to be used as agents for the purification of proteins and nucleic acid without disrupting their function, as controlled delivery agents for sensitive physiologically active molecules, and as injectable scaffolds. Despite this advantage, there have been far fewer reports in literature on thermoresponsive coacervate-type polymers as compared to coil-globule type polymers.
Polymeric degradation is a desirable quality for numerous medical applications but is not achievable with many common thermoresponsive polymers, such as polyacrylamides. Polyamides and synthetic poly(amino acids) exhibit biodegradation due to the gradual hydrolysis of the amide backbone. However, the slow degradation may be limiting for applications where a faster degrading material, such as those based on a more hydrolysable ester bond, would be desirable. Thermoresponsive polyphosphoesters and polyesters do exist in the literature, but suffer from limited side chain functionality and few are able to form coacervates.
Thus, there presently exists a need in the art to for a biodegradable, theroresponsive polymers.